Molecular analysis of duodenal carcinogenesis
| Project/Area Number |
20K07401
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 49020:Human pathology-related
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| Research Institution | National Cancer Center Japan |
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Principal Investigator |
Shigeki Sekine 国立研究開発法人国立がん研究センター, 中央病院, 医長 (10321879)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 十二指腸 / 腺腫 / 腺癌 / 発癌過程 |
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| Outline of Research at the Start |
本研究は非浸潤性病変から十二指腸癌に至る発生経路の多様性を形態および分子病理学的解析により明らかにすることを目的とする。このため、十二指腸癌発生の各段階にあたる、異所性胃上皮・腺腫・腺癌を対象として、遺伝子異常と病理学的所見の統合的な解析を行うことで、十二指腸腫瘍の進展のそれぞれの段階における形態的特徴と遺伝子変異の関係を検索し、十二指腸癌進展のモデル作成を目指す。
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| Outline of Final Research Achievements |
A total of 144 duodenal adenomas and 54 adenocarcinomas were subjected to analysis for immunohistochemical phenotypes, mismatch repair status, and genetic alterations. It was observed that APC mutations were frequent in adenomas but rare in adenocarcinomas, indicating that clinically detected adenomas were generally associated with a low risk of malignant progression. Furthermore, distinct genetic alterations were found in specific adenoma subtypes, supporting the validity of the current morphological classification. Notably, GNAS mutations were identified as a genetic characteristic of gastric-type adenomas and adenocarcinomas. Additionally, a high frequency of mismatch repair deficiency was observed in adenocarcinomas, underscoring the clinical significance of mismatch repair deficiency testing.
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| Academic Significance and Societal Importance of the Research Achievements |
現在臨床的に切除されている十二指腸腺腫の多くが、比較的浸潤癌への進展リスクの低い病変であることが示唆された。また、十二指腸発癌の発生経路の分子生物学的多様性がより明らかになった。十二指腸癌はミスマッチ修復異常を示す腫瘍の頻度が高く、その検索の臨床的意義が高いと考えられた。
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Report
(4 results)
Research Products
(1 results)
